1. Field of the Invention
The present invention relates generally to the aspiration and dispensing of microfluidic quantities of fluid and, in particular, to a feedback control system for controlling and monitoring the operation of aspirate-dispense systems to provide optimal, efficient and versatile operation and performance.
2. Description of the Related Art
There is an ongoing effort, both public and private, to spell out the entire human genetic code by determining the structure of all 100,000 or so human genes. Also, simultaneously, there is a venture to use this genetic information for a wide variety of genomic applications. These include, for example, the creation of microarrays of DNA material on substrates to create an array of spots on microscope slides or biochip devices. These arrays can be used to read a particular human""s genetic blueprint. The arrays decode the genetic differences that make one person chubbier, happier or more likely to get heart disease than another. Such arrays could detect mutations, or changes in an individual""s chemical or genetic make-up, that might reveal something about a disease or a treatment strategy.
One typical way of forming DNA microarrays utilizes an aspirate-dispense methodology. An aspirate-dispense system aspirates (xe2x80x9csucksxe2x80x9d) reagent(s) from a source of single strands of known DNA and dispenses (xe2x80x9cspitsxe2x80x9d) them on one or more targets to form one or more DNA arrays. Typically, an unknown sample of DNA is broken into pieces and tagged with a fluorescent molecule. These pieces are poured onto the array(s); each piece binds only to its matching known DNA xe2x80x9czipperxe2x80x9d on the array(s). The handling of the unknown DNA sample may also utilize an aspirate and/or dispense system. The perfect matches shine the brightest when the fluorescent DNA binds to them. Usually, a laser is used to scan the array(s) for bright, perfect matches and a computer ascertains or assembles the DNA sequence of the unknown sample.
Microfluidic aspirate-dispense technology also has a wide variety of other research and non-research related applications in the biodiagnostics, pharmaceutical, agrochemical and material sciences industries. Aspirate-dispense systems are utilized in drug discovery, high throughput screening, live cell dispensing, combinatorial chemistry and test strip fabrication among others. These systems may be used for compound reformatting, wherein compounds are transferred from one plate source, typically a 96 microwell plate, into another higher density plate such as a 384 or 1536 microwell plate. Compound reformatting entails aspirating sample from the source plate and dispensing into the target plate. In these and other applications it is desirable, and sometimes crucial, that the aspirate-dispense system operate efficiently, accurately and with minimal wastage of valuable reagents.
Conventional aspirate-dispense technologies and methods are well known in the art, for example, as disclosed in U.S. Pat. No. 5,743,960, incorporated herein by reference. These typically use pick-and-place (xe2x80x9csuck-and-spitxe2x80x9d) fluid handling systems, whereby a quantity of fluid is aspirated from a source and dispensed onto a target for testing or further processing. But to efficiently and accurately perform aspirate and dispense operations when dealing with microfluidic quantities, less than 1 microliter (xcexcL), of fluid can be a very difficult task. The complexity of this task is further exacerbated when frequent transitions between aspirate and dispense functions are required. Many applications, such as DNA microarraying, can involve a large number of such transitions.
Conventional aspirate-dispense technology, when applied at these microfluidic levels, can suffer from unrepeatable, inconsistent and slow performance, and also result in wastage of valuable reagent. This is especially true at start-up and during transient or intermittent operations. Moreover, conventional aspirate-dispense systems can be limited in their adaptability, for example, in providing a sufficiently quick response to changes in the desired fluid output.
Therefore, there is a need for improved technology and methodology that provides for efficient, repeatable, accurate and versatile aspirate-dispense operations when handling and transferring fluids in microfluidic quantities, while reducing wastage of such fluids.
The present invention overcomes some or all of the above limitations by providing a state-variable feedback control system for monitoring and optimally controlling the operation of a microfluidic aspirate dispense-system. A steady state operating pressure is determined from the fluid, flow and/or operational characteristics of the system. Measurements from one or more pressure sensors are part of the control strategy to derive information for active feedback control and/or to achieve the desired operating pressure. Advantageously, the control system adds to the versatility of the aspirate-dispense system, for example, by permitting rapid dispensing of drops of different size. The control system also desirably facilitates efficient, repeatable and accurate performance and reduces wastage of valuable reagents or fluid.
In accordance with one embodiment, the invention provides a method of actively controlling a fluid delivery system. The fluid delivery system generally comprises a dispenser hydraulically arranged in series with a direct current fluid source. The method comprises the step of determining a steady state dispense pressure based on the fluid dynamical characteristic equations of the system. The direct current fluid source is operated to cause the steady state dispense pressure to exist within the system. The dispenser and the direct current fluid source are then actuated to dispense precise and/or predetermined quantities of a fluid onto a target.
For purposes of summarizing the invention and the advantages achieved over the prior art, certain objects and advantages of the invention have been described herein above. Of course, it is to be understood that not necessarily all such objects or advantages may be achieved in accordance with any particular embodiment of the invention. Thus, for example, those skilled in the art will recognize that the invention may be embodied or carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objects or advantages as may be taught or suggested herein.
All of these embodiments are intended to be within the scope of the invention herein disclosed. These and other embodiments of the present invention will become readily apparent to those skilled in the art from the following detailed description of the preferred embodiments having reference to the attached figures, the invention not being limited to any particular preferred embodiment(s) disclosed.